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BackgroundThe Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER, NCT04272801) trial aims to determine whether 3 months of preoperative endocrine therapy (pre-ET) informs adjuvant radiation therapy decisions among older women with early stage, ER-positive breast cancer. We propose the POWER Pathologic Assessment and Ki-67 (POWER-PAK) scoring system to characterize the histologic effects of pre-ET.MethodsHistologic evaluation was performed on core biopsy and lumpectomy specimens from 37 POWER trial participants who completed pre-ET and surgery. The POWER-PAK score consists of tumor regression, decrease in Ki-67 expression, and ER expression, each ranging from 0 to 2. Scores were aggregated to create the POWER-PAK score with a range from 0 to 6. Participants with no residual tumor were labelled 6-NRT.ResultsER expression did not decrease after pre-ET. Ki-67 decreased from 13% in biopsy specimens to 5% in the lumpectomy specimens (p < 0.001). Cellularity decreased from 40% to 23% (p < 0.001). There was heterogeneity of POWER-PAK scores ranging from 2 to 6-NRT: score of 2, n = 2 (5.4%); 4, n = 8 (21.6%); 5, n = 4 (10.8%); 6, n = 16 (43.2%); and 6-NRT, n = 7 (18.9%). Participants with a score ≥ 5 were more likely to have smaller tumors after pre-ET compared with those with a score < 5 (p = 0.04).ConclusionsThe tumor responses following treatment with pre-ET are heterogenous. We propose that the POWER-PAK scoring system can be used to quantify response to pre-ET. Future studies will explore the use of POWER-PAK to support informed decision-making for adjuvant therapy options for older women with early stage breast cancer.

PurposeSexual side effects after breast cancer treatment are common and distressing to both survivors and their intimate partners, yet few receive interventions to address cancer-related sexual concerns. To direct intervention development, this qualitative study assessed the perceptions of female breast cancer survivors, intimate partners of breast cancer survivors, and breast cancer oncology providers about how an Internet intervention for couples may address breast cancer-related sexual concerns.MethodsSurvivors (N = 20) responded to online open-ended surveys. Partners (N = 12) and providers (N = 8) completed individual semi-structured interviews. Data were inductively coded using thematic content analysis.ResultsThree primary intervention content areas were identified by the key stakeholder groups: (1) information about and strategies to manage physical and psychological effects of cancer treatment on sexual health, (2) relationship and communication support, and (3) addressing bodily changes and self-image after treatment. Survivors and partners tended to express interest in some individualized intervention private from their partner, although they also emphasized the importance of opening communication about sexual concerns within the couple. Survivors and partners expressed interest in an intervention that addresses changing needs across the cancer trajectory, available from the time of diagnosis and through survivorship.ConclusionInternet intervention for couples to address cancer-related sexual concerns, particularly one that provides basic education about treatment side effects and that evolves with couples’ changing needs across the cancer trajectory, was perceived as a valuable addition to breast cancer care by survivors, partners, and providers.

Purpose Ensuring there are clear standards for addressing cancer-related sexual side effects is important. Currently, there are differences in two leading sets of clinical guidelines regarding the inclusion of survivors’ romantic partners into clinical discussions between survivors and their providers about this issue. To help refine guidelines, we examine breast cancer survivor, partner, and oncology provider perspectives about including partners in discussions about cancer-related sexual side effects in a secondary analysis of a broader qualitative study. Methods Partnered female breast cancer survivors ( N  = 29) completed online surveys, and intimate partners of breast cancer survivors ( N  = 12) and breast oncology providers ( N  = 8) completed semi-structured interviews. Themes were derived from thematic content analysis. Results Among survivors who reported a discussion with their provider, fewer than half indicated their partner had been present, despite most survivors expressing it was — or would have been — helpful to include their partner. Partners also largely indicated being included was or would have been helpful, when welcomed by the survivor. Providers similarly emphasized the importance of survivors’ autonomy in deciding whether to discuss sexual concerns in the presence of a partner. Conclusions Partners were infrequently included in conversations about cancer-related sexual side effects, even though survivors, partners, and providers alike expressed value in these discussions occurring with the couple together — when that is the survivor’s preference. Findings suggest future clinical guidelines should emphasize that incorporating partners into clinical discussions about sexual concerns is important for many breast cancer patients. Soliciting and enacting patients’ preferences is essential for truly patient-centered care.

Prospective randomized data supports radiation omission in women ≥ 65 years who take adjuvant endocrine therapy (AET) following breast-conserving surgery. Many patients who omit radiation stop AET early due to side effects. In the POWER trial, a prospective single-arm study, patients took 90 days of pre-operative endocrine therapy (pre-ET) to assess tolerance before making adjuvant treatment decisions. We hypothesized that patient-reported outcomes (PROs) during pre-ET would be heterogeneous and that 90 days was sufficient time for symptoms to develop.BACKGROUNDProspective randomized data supports radiation omission in women ≥ 65 years who take adjuvant endocrine therapy (AET) following breast-conserving surgery. Many patients who omit radiation stop AET early due to side effects. In the POWER trial, a prospective single-arm study, patients took 90 days of pre-operative endocrine therapy (pre-ET) to assess tolerance before making adjuvant treatment decisions. We hypothesized that patient-reported outcomes (PROs) during pre-ET would be heterogeneous and that 90 days was sufficient time for symptoms to develop.PRO data from POWER trial participants was obtained before, during, and after pre-ET, including health-related quality of life (HRQoL), depression, and ET symptoms using the EORTC-QLQ, CESD-R, and BCPT-SCL tools. PRO assessments were further analyzed after stratifying patients by high or low perceived sensitivity to medicine (PSM).PATIENTS AND METHODSPRO data from POWER trial participants was obtained before, during, and after pre-ET, including health-related quality of life (HRQoL), depression, and ET symptoms using the EORTC-QLQ, CESD-R, and BCPT-SCL tools. PRO assessments were further analyzed after stratifying patients by high or low perceived sensitivity to medicine (PSM).Pre-ET PROs were assessed for 75 participants. The majority (73.3%) reported symptoms during pre-ET. Only 10.7% had symptoms severe enough to stop pre-ET before 90 days. Vasomotor (42.7%) and musculoskeletal (41.3%) symptoms were the most common. HRQoL was preserved for 66.6% participants. Patients with high PSM had more ET side effects.RESULTSPre-ET PROs were assessed for 75 participants. The majority (73.3%) reported symptoms during pre-ET. Only 10.7% had symptoms severe enough to stop pre-ET before 90 days. Vasomotor (42.7%) and musculoskeletal (41.3%) symptoms were the most common. HRQoL was preserved for 66.6% participants. Patients with high PSM had more ET side effects.Patients developed similar side effects during pre-ET as those typically seen with AET. PROs and the impact of pre-ET on HRQoL were patient-dependent. A 90-day course of pre-ET is sufficient for patients to develop symptoms reflective of long-term AET. Future analyses will assess the association of pre-ET PROs with AET initiation and adherence.CONCLUSIONPatients developed similar side effects during pre-ET as those typically seen with AET. PROs and the impact of pre-ET on HRQoL were patient-dependent. A 90-day course of pre-ET is sufficient for patients to develop symptoms reflective of long-term AET. Future analyses will assess the association of pre-ET PROs with AET initiation and adherence.

The treatment landscape of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer has evolved dramatically in recent years. While the combination of endocrine therapy and a cyclin-dependent kinase 4/6 inhibitor is accepted as standard first-line treatment in most settings without visceral crisis, newer therapies have challenged traditional treatment models where cytotoxic chemotherapy was previously felt to be the only second-line option at time of progression. The incorporation of next-generation sequencing has led to the identification of molecular targets for therapeutic agents, including phosphatidylinositol 3-kinase and ESR1 , though similar pathways can be targeted even in the absence of a mutation, such as with use of inhibitors of mammalian target of rapamycin. Current data also supports the use of cyclin-dependent kinase inhibitors beyond progression, even prior to the patient’s first introduction to chemotherapy. The abundance of therapeutic options not only delay time to cytotoxic chemotherapy and antibody–drug conjugate initiation, but has resulted in improvement in breast cancer survivorship. Many unanswered questions remain, however, as to the most efficacious way to sequence these novel agents. To assist in this decision-making, we will review the existing data on systemic therapy and propose a treatment paradigm.

Abstract Background Prospective randomized data supports radiation omission in women ≥65 years who take adjuvant endocrine therapy (AET) following breast-conserving surgery. Many patients who omit radiation stop AET early due to side effects. In the POWER trial, a prospective single-arm study, patients took 90 days of preoperative endocrine therapy (pre-ET) to assess tolerance before making adjuvant treatment decisions. We hypothesized that patient-reported outcomes (PROs) during pre-ET would be heterogeneous and that 90 days was sufficient time for symptoms to develop. Patients and Methods PRO data from POWER trial participants was obtained before, during, and after pre-ET, including health-related quality of life (HRQoL), depression, and ET symptoms using the EORTC-QLQ, CESD-R, and BCPT-SCL tools. PRO assessments were further analyzed after stratifying patients by high or low perceived sensitivity to medicine (PSM). Results Pre-ET PROs were assessed for 75 participants. The majority (73.3%) reported symptoms during pre-ET. Only 10.7% had symptoms severe enough to stop pre-ET before 90 days. Vasomotor (42.7%) and musculoskeletal (41.3%) symptoms were the most common. HRQoL was preserved for 66.6% of participants. Patients with high PSM had more ET side effects. Conclusions Patients developed similar side effects during pre-ET as those typically seen with AET. PROs and the impact of pre-ET on HRQoL were patient-dependent. A 90-day course of pre-ET is sufficient for patients to develop symptoms reflective of long-term AET. Future analyses will assess the association of pre-ET PROs with AET initiation and adherence.

Checkpoint inhibitors (CPIs) and pegfilgrastim, a long-acting growth factor agent, are vital components of current cancer treatments. Immune-related adverse events (irAEs) such as colitis and pneumonitis are well-established toxicities associated with CPI therapy. However, large-vessel vasculitis secondary to CPI utilization is reported only in rare case reports and case series. Interestingly, large-vessel vasculitis has also been reported as a rare complication of pegfilgrastim use. We present a 59-year-old female with left stage IIA (cT2N0M0) triple-negative breast cancer receiving neoadjuvant decitabine and pembrolizumab prior to neoadjuvant chemotherapy (NAC). NAC included standard-of-care dose dense doxorubicin and cyclophosphamide (ddAC) supported with pegfilgrastim use followed by weekly carboplatin and paclitaxel. After receiving her second cycle of ddAC with pegfilgrastim, the patient reported five days of left shoulder and arm pain. Subsequent CT imaging demonstrated wall thickening and inflammatory changes surrounding the left subclavian artery, aortic arch, left carotid artery, proximal innominate arteries, and the mid internal carotid arteries and its branching vessels. These findings were extremely concerning for large-vessel vasculitis. Excluding CPI therapy and pegfilgrastim use, no additional inciting event or medication that the patient was exposed to was noted to be associated with large-vessel vasculitis. We present this case to report on this rare but severe complication from commonly utilized agents in cancer treatment. We also extend the possibility of large-vessel vasculitis development in relation to the COVID-19 vaccine due to shared ingredients found in both the vaccine and pegfilgrastim. It is important to outline the treatment used for such a complication as no standardized treatment has been established for large-vessel vasculitis caused by CPI therapy or pegfilgrastim use.

Background. Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial. Methods. A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2-negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3 mg to 5 mg and capecitabine 800 mg/m2 to 1000 mg/m2. Results. Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar-plantar dysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a prespecified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase, due to drug supply limitations. Conclusion. The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer. This study’s clinical investigation of entinostat in breast cancer was halted, but drug development of this agent continues outside the US. There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.

Breast cancer is a common, survivable malignancy affecting women. With improved survival, the off‐target effects of chemotherapy, such as a decline in cardiorespiratory fitness and worse cardiovascular outcomes, have been recognized. Exercise training may help mitigate these effects. In this study, patients with breast cancer ( N = 24) scheduled to undergo chemotherapy were randomized to either remotely administered high‐intensity interval training (HIIT) or moderate‐intensity exercise (MOD) based on ACSM guidelines for cancer survivors. HIIT involved three weekly sessions using the 4 × 4 protocol at 85%–90% peak heart rate (PHR), while MOD consisted of 150 min per week at 70%–75% PHR. Exercise training began 1–2 weeks before chemotherapy and continued throughout treatment. Baseline testing was conducted prior to chemotherapy and follow‐up testing 7–10 days after completion. Assessments included VO 2peak , echocardiography, vascular function, and blood biomarkers. VO 2peak significantly declined in MOD ( n = 8; 1.50 ± 0.23 to 1.27 ± 0.28 L/min; p = 0.013, d = 1.2), while remaining stable in HIIT ( n = 7; 1.58 ± 0.24 to 1.52 ± 0.28 L/min; p = 0.445, d = 0.3), with a large between‐group effect size ( p = 0.109, d = 0.9). NTproBNP levels significantly increased in MOD (104.3 ± 35.1 to 158.1 ± 56.0; p = 0.018), but not in HIIT. The study was underpowered due to greater than anticipated dropout to detect significant between‐group differences in VO 2peak . These data have implications for the design of scalable exercise interventions in patients undergoing chemotherapy for breast cancer.